The role of area deprivation index in health care disruptions among cancer survivors during the SARS-CoV-2 pandemic.

OBJECTIVE: To examine the associations between demographic/medical and geographic factors with follow-up medical care and health-related quality of life (HRQoL) among cancer survivors during the SARS-CoV-2 pandemic. STUDY DESIGN: Cross-sectional survey. METHODS: An online survey was sent to cancer survivors between May 2020 and January 2021, exploring their experience with SARS-CoV-2, follow-up care, and HRQoL. PolicyMap was used to geocode home addresses. Both geographic and demographic/medical factors were examined for their associations with SARS-CoV-2 experience, follow-up care, and HRQoL (FACT-G7). RESULTS: Geographic data were available for 9651 participants. Patients living in the highest area deprivation index (ADI) neighborhoods (most deprived) had higher odds of avoiding in-person general (odds ratio [OR] = 7.20; 95% confidence interval [CI] = 2.79-18.60), cancer (OR = 8.47; 95% CI = 3.73-19.30), and emergency (OR = 14.2; 95% CI = 5.57-36.30) medical care, as well as lower odds of using telemedicine (OR = 0.61; 95% CI = 0.52-0.73) compared to the lowest ADI group. Race/ethnicity was not associated with follow-up care after controlling for ADI. The effect of ADI on HRQoL was generally in the expected direction, with higher ADI being associated with worse HRQoL. CONCLUSIONS: ADI influenced follow-up medical care more than age, race/ethnicity, or health insurance type. Healthcare providers and institutions should focus on decreasing barriers to in-person and telemedicine health care that disproportionally impact those living in more deprived communities, which are exacerbated by health care disruptions like those caused by the SARS-CoV-2 pandemic.

Superoxide levels and function of cerebral blood vessels after inhibition of CuZn-SOD.

The goal of this study was to examine the role of endogenous copper/zinc (CuZn)-superoxide dismutase (SOD) on superoxide levels and on responses of cerebral blood vessels to stimuli that are mediated by nitric oxide (acetylcholine) and cyclooxygenase-dependent mechanisms (bradykinin and arachidonic acid). Levels of superoxide in the rabbit basilar artery were measured using lucigenin-enhanced chemiluminescence (5 microM lucigenin). Diethyldithiocarbamate (DDC; 10 mM), an inhibitor of CuZn-SOD, increased superoxide levels by approximately 2.4-fold (P < 0.05) from a baseline value of 1.0 +/- 0.2 relative light units x min(-1) x mm(-2) (means +/- SE). The diameter of cerebral arterioles (baseline diameter, 99 +/- 3 microm) was also measured using a closed cranial window in anesthetized rabbits. Topical application of DDC attenuated responses to acetylcholine, bradykinin, and arachidonate, but not nitroprusside. For example, 10 microM arachidonic acid dilated cerebral arterioles by 40 +/- 5 and 2 +/- 2 microm under control conditions and after DDC, respectively (P < 0.05). These inhibitory effects of DDC were reversed by the superoxide scavenger 4,5-dihydroxy-1,3-benzenedisulfonic acid (10 mM). Arachidonate increased superoxide levels in the basilar artery moderately under normal conditions and this increase was greatly augmented in the presence of DDC. These findings suggest that endogenous CuZn-SOD limits superoxide levels under basal conditions and has a marked influence on increases in superoxide in vessels exposed to arachidonic acid. The results also suggest that nitric oxide- and cyclooxygenase-mediated responses in the cerebral microcirculation are dependent on normal activity of CuZn-SOD.

Effects of free radicals and leukocytes on increases in blood-brain barrier permeability during colitis.

This study examined the role of leukocytes and free radicals on increases in permeability of the blood-brain barrier (BBB) in rabbits with acute colitis. Trinitrobenzene sulfonic acid (TNBS) was used to induce colitis in male New Zealand White rabbits. The extraction ratio of fluorescein was used as an index of the permeability of the BBB. The extraction ratio for fluorescein was 1.0 x 10(-3) +/- 2 x 10(-4) ml/g and 1.1 x 10(-3) +/- 3 x 10(-4)ml/g (mean +/- SE) for saline (N = 7) and ascorbic acid-treated (N = 8) rabbits with sham colitis. Conversely, TNBS-induced acute colitis increased the extraction ratio over 70% in saline (N = 8) and ascorbic acid-treated (N = 8) animals. Vinblastine significantly reduced the number of circulating leukocytes, whereas the permeability of the BBB was augmented by 54% in rabbits with TNBS-induced acute colitis (N = 8). Vinblastine had no effect on the permeability of the BBB in rabbits with sham colitis (N = 8). These data suggest that free radicals are not responsible for BBB disruption, and leukocytes may protect the BBB during acute colitis.

Experimental colitis increases blood-brain barrier permeability in rabbits.

Extraintestinal manifestations of inflammatory bowel disease are numerous. This study examined the effects of two models of acute colitis on cerebral blood flow (CBF) and permeability of the blood-brain barrier in rabbits. CBF (measured with radiolabeled microspheres), or the extraction ratio or permeability-surface area (PS) product of the blood-brain barrier to fluorescein and FITC-dextran, was measured 48 h after colitis induction with acetic acid (HAc) or trinitrobenzene sulfonic acid (TNBS). PS product for fluorescein increased (P < 0.05) in TNBS colitis (1.33 x 10(-5) +/- 0.52 x 10(-5) ml/s and 0.48 x 10(-5) +/- 0.13 x 10(-5) ml/s (mean +/- SE) for treated (n = 14) and untreated (n = 10) animals, respectively. PS product for the larger FITC-dextran was not different in TNBS colitis (0.24 x 10(-5) +/- 0.09 x 10(-5) ml/s, n = 7) compared with untreated controls (0.19 x 10(-5) +/- 0.04 x 10(-5) ml/s, n = 8). PS product for fluorescein increased (P < 0.01) in HAc colitis compared with vehicle (2.66 x 10(-5) +/- 1.46 x 10(-5) ml/s and 0.33 x 10(-5) +/- 0.05 x 10(-5) ml/s, respectively; n = 6 in each group). The extraction of fluorescein from the blood to the brain increased by 75% during TNBS colitis when compared with vehicle (P < 0.05). CBF and cerebrovascular resistance did not change from the untreated control after TNBS colitis. Our data suggest that, irrespective of induction method, acute colitis increases the permeability of the blood-brain barrier to small molecules without changing CBF.

Temporal patterns of colonic blood flow and tissue damage in an animal model of colitis.

This study tested the hypothesis that altered colonic blood flow may contribute to tissue damage during the development of colitis in the rabbit. This was achieved by using radioactive microspheres to measure colonic blood flow at various times after colitis induction with trinitrobenzene sulfonic acid. Significant colonic damage occurred 6 hours post colitis induction and persisted throughout the 5 day study. Blood flow to the muscularis propria and mucosa/muscularis mucosae compartments increased significantly from 5 minutes until one hour post induction. At 6 and 12 hours post induction colonic blood flow returned to control levels before increasing again from 24 to 96 hours. This second increase in flow was, however, predominantly in the mucosa/muscularis mucosae compartment. Blood flow in the stomach and non-gastrointestinal tissues did not change significantly at any time. These data demonstrate that increased colonic blood flow may be disrupted in the early stages of colitis and that this coincides with the onset of significant damage. It is concluded that maintenance of elevated colonic blood flow throughout the development of colitis may help to ameliorate subsequent tissue injury.

Low power, type II errors, and other statistical problems in recent cardiovascular research.

Frequently in biomedical literature, measurements are considered "not statistically different" if a statistical test fails to achieve a P value that is < or = 0.05. This conclusion may be misleading because the size of each group is too small or the variability is large, and a type II error (false negative) is committed. In this study, we examined the probabilities of detecting a real difference (power) and type II errors in unpaired t-tests in Volumes 246 and 266 of the American Journal of Physiology: Heart and Circulatory Physiology. In addition, we examined all articles for other statistical errors. The median power of the t-tests was similar in these volumes (approximately 0.55 and approximately 0.92 to detect a 20% and a 50% change, respectively). In both volumes, approximately 80% of the studies with nonsignificant unpaired t-tests contained at least one t-test with a type II error probability > 0.30. Our findings suggest that low power and a high incidence of type II errors are common problems in this journal. In addition, the presentation of statistics was often vague, t-tests were misused frequently, and assumptions for inferential statistics usually were not mentioned or examined.

Autoregulation of blood flow to choroid plexus of rabbits.

Blood flow to the choroid plexus (CP) of rabbits was measured before and during an increase in arterial pressure (AP). Blood flow returned to control levels in the CP of the lateral and fourth ventricles of the brain when AP was increased 63% by i.v. infusion of norepinephrine. However, when AP was increased 68% by occlusion of the descending thoracic aorta, blood flow to the CP of the fourth ventricle remained elevated, while blood flow to the CP of the lateral ventricles returned to the control level. Our findings suggest that blood flow to the CP of the lateral ventricles autoregulates during nonpharmacological or pharmacological increases in AP, while blood flow to CP of the fourth ventricle does not autoregulate during nonpharmacological increases in AP.